Experiments presented in this proposal are designed to investigate the immunochemistry of epidermal growth factor (EGF) in rat brain. Quantitation and localization of EGF in rat brain will be determined using radioimmunoassay (RIA) in conjunction with immunocytochemistry (ICC) with an homologous antibody prepared against pure rat EGF (which is available). Using the abovementioned techniques, distribution and levels of EGF in various regions of the brain will be determined in male and female rats at various prenatal ages, at various early postnatal ages and at maturity. These experiments will be undertaken both to determine the distribution and levels of EGF in the brain, and to determine the age (time) of appearance of EGF in the brain of developing animals. In addition, distribution of the EGF-receptor (EGF-R) will be determined by ICC in mature rat brains. The effects of sex hormones on brain EGF levels and distribution will be determined in adult male and female animals in different hormonal states. RIA and ICC techniques will be performed on brains of animals that have been surgically neutered, and on animals that have been surgically neutered and have received replacement of the sex hormone. Attempts will be made to demonstrate de novo synthesis of EGF by the brain by incorporation of radioactive amino acids into the immunoreactive material. The physicochemical properties of EGF-like material in rat brain will be examined and comparisons made with authentic rat submandibular gland EGF. These proposed studies may implicate EGF as playing a role in development of the brain and as a brain neurotransmitter- neuromodulator.